The purpose of this research proposal is to investigate the mechanism and site(s) of action(s) of the neurotransmitter, dopamine, in the modulation of prolactin and growth hormone secretion and synthesis. This will be accomplished by determining the effects of central (L-dopa plus carbidopa) and peripheral (dopamine infusion) dopamine augmentation on basal and peripherally stimulated (TRH) and centrally stimulated (hypoglycemia, sleep) hormonal release. We will determine whether patients with hypersecretion of growth hormone or prolactin have a qualitative or quantitative abnormality in their response to these maneuvers by comparing them to normal volunteers and to patients with hyperprolactinemia due to surgical or functional pituitary stalk section. The hormonal effects will be correlated with dopamine levels measured radioenzymatically. In vitro studies using pituitary cell cultures will be used to investigate the local control of prolactin synthesis and secretion. The mutual interaction of dopamine and TRH will be studied and the effects of thyroid hormone, estrogen and glucocorticoids on these interactions will be ascertained. The cell culture system will be used to determine whether plasmas obtained during our pharmacologic manipulations have releasing or inhibiting activity. The contribution of dopamine to these activities will be determined. Our observations that normal human serum contains apparently large molecular weight constituents which stimulate prolactin secretion in vitro will be pursued further to determine if they have a physiologic role and to purify and characterize them.